Evolution of New cis-Regulatory Motifs Required for Cell-Specific Gene Expression in Caenorhabditis
Barkoulas et al. PLoS Genet 2016 Sep; 12(9):e1006278
PMID: 27588814 DOI: 10.1371/journal.pgen.1006278
Gupta B: F1000Prime Recommendation of [Barkoulas M et al., PLoS Genet 2016, 12(9):e1006278].
In F1000Prime, 20 Sep 2016; DOI: 10.3410/f.726706285.793523035.
Comparative studies have shown that changes in cis-regulatory sequences contribute to gene expression differences. However, cis evolution may also occur without altering gene expression.
In this paper, authors have investigated the regulation of lin-3 (EGF-family) in Rhabditidae nematode species, and report significant cis changes within a 58-bp cell-specific enhancer fragment even though the enhancer activates lin-3 expression in a conserved manner.
lin-3 was originally identified in Caenorhabditis elegans and shown to encode for a secreted EGF ligand that induces vulva formation. The ligand is produced by a specialized cell in the gonad, termed anchor cell. The findings show that the 58-bp region has undergone cis evolutionary changes in nematodes, resulting in the turnover of major transcription factor binding sites. Heterologous transgene expression studies involving C. elegans and two distant species C. angaria and C. afra uncovered compensatory evolution in lin-3 enhancer.
What makes this work more interesting is the in vivo quantification of cell-specific transcription and the use of CRISPR/Cas9 genome editing technology in a multicellular organism to manipulate endogenous gene expression.